Importance: Opioid addiction affects approximately 2.4 million Americans. Nearly 1 million individuals, including a growing subset of 21000 minors, abuse heroin. Its annual cost within the United States amounts to $51 billion. Inhaled heroin use represents a global phenomenon and is approaching epidemic levels east of the Mississippi River as well as among urban youth. Chasing the dragon (CTD) by heating heroin and inhaling its fumes is particularly concerning, because this method of heroin usage has greater availability, greater ease of administration, and impressive intensity of subjective experience (high) compared with sniffing or snorting, although it also has a safer infectious profile compared with heroin injection. This is relevant owing to peculiar and often catastrophic brain complications. Following the American Medical Association Opioid Task Force mandate, we contribute a description of the pharmacology, pathophysiology, clinical spectrum, neuroimaging, and neuropathology of CTD leukoencephalopathy, as distinct from other heroin abuse modalities. Observations: The unique spectrum of CTD-associated health outcomes includes an aggressive toxic leukoencephalopathy with pathognomonic neuropathologic features, along with sporadic instances of movement disorders and hydrocephalus. Clinical CTD severity is predominantly moderate at admission, frequently unmodified at discharge, and largely improved in the long term. Mild cases survive with minor sequelae, while moderate to severe presentations might deteriorate and progress to death. Other methods of heroin use may complicate with stroke, seizure, obstructive hydrocephalus, and (uncharacteristically) leukoencephalopathy. Conclusions and Relevance: The distinct pharmacology of CTD correlates with its specific clinical and radiological features and prompts grave concern for potential morbidity and long-term disability costs. Proposed diagnostic criteria and standardized reporting would ameliorate the limitations of CTD literature and facilitate patient selection for a coenzyme Q10 therapeutic trial.